Pharmacologic
Management

Cognitive enhancers and memantine may have a role to play in the treatment of BPSD. They may also contribute to the development of BPSD. If a patient presents with BPSD and is currently taking a cognitive enhancer and/or memantine, efforts should be made to determine if there may be a temporal association between the initiation of treatment and the emergence of BPSD. If a patient with BPSD is not yet taking a cognitive enhancer or memantine, then the addition of a cognitive enhancer or memantine should occur as one of the final steps in symptom management and only after the most pressing behavioral symptoms have been successfully addressed. A cognitive enhancer or memantine should be added sequentially and only after it has been confirmed that the addition of the first medication has not caused problems.

Namenda® (memantine) has been shown in clinical trials to have effects on cognition and behavior in moderate to severe Alzheimer’s disease (AD), as mono therapy or when added to a cholinesterase inhibitor. These effects are small. There were no benefits over placebo in clinical trials of mild AD. Some studies (not controlled clinical trials) suggest that long-term use of the combination of a cholinesterase inhibitor and memantine has benefits on cognition in people with AD that may be sustained over years. Memantine is generally well-tolerated.

Psychotropic Medication Management

It is important for clinicians involved with the assessment and treatment of BPSD to remember that with only rare exceptions, most types of dementia are progressive neurocognitive illnesses which means that the underlying disease process leads to ever increasing damage to the afflicted individual’s brain. This reality sometimes leads to worsening behavioral challenges but sometimes leads to improvement in problem behaviors whenever the brain tissue centrally involved in triggering the behavior is damaged and no longer able to play a causal role in the behavior’s occurrence. Once a patient with BPSD has been stable for 3-6 months, if psychotropic medication have been required to manage the behavior, it is then important to initiate a cautious, incremental reduction in psychotropic medication and monitor the patient closely. If the problem behavior(s) does (do) not reappear after several weeks, then another reduction should occur. On the other hand, if at any point a reduction leads to the return of a problem behavior, then the patient should be returned to the dose at which the problem behavior remained in remission.

Here is a handout with specific medications, usage and dosage.

Pharmacologic Treatment: General Principles

• Start low, go slow and determine lowest effective dose, or
• Start low, increase relatively swiftly and then be prepared for the need to back off in order to determine lowest effective dose,
• Withdraw after an appropriate period and observe for relapse,
• Behavioral symptoms vary according to stage of illness and may remit as the illness progresses,
• Refer to the PDR or comparable reference for information on introducing and titrating medication.

Categories of Medications Which May be Helpful

• Alpha adrenergic blockers
• Antipsychotics
• Antidepressants
• Anxiolytics
• Beta blockers
• Cholinesterase inhibitors
• Dextromethorphan-quinidine
• Hormones
• Memantine
• Mood stabilizers
• Pain medications- especially routine acetaminophen

Benzodiazephines

Short-acting, renally excreted agents are preferred

• Lorazepam (Ativan®)
• Oxazepam (Serax®)

Trazodone (Desyrel®)
There is no good data for the use of this medication based on Cochran Reports

Other Medications That May Prove Helpful

Prazosin (Minipress®)

The nonadrenergic system is the brain “adrenalin” system for attention and arousal. Excessive noradrenergic reactivity produces anxiety and agitation, and contributes to agitation in AD.

Dextromethoraphane/quinidine

• Dextromethorphane hydrobromide and quinidine sulfate (Nuedexta®) is approved for pseudobulbar affect (PBA) in the US and European Union

• Dextromethorphane is most well-known as a cough suppressant
  • a low low-affinity, uncompetitive NMDA receptor antagonist
  • σ₁ (sigma₁) receptor agonist
  • Serotonin and norepinepherine reuptake inhibitor
  • Neuronal nicotinic α₃β₄ receptor antagonist
• Quinidine is a Class 1 antiarrhythmic
  • When combined with dextromethorphan, quinidine works by increasing the amount of dextromethorphan in the body

Avoiding Suboptimal Prescribing and Polypharmacy

For any indication, use the medicine most appropriate for an older patient and avoid:

• Polypharmacy (too many medications) and the prescribing cascade
• Prescribing a medication from an essential category of medication that is not senior friendly
• Prescribing a dose of an essential medication that is larger than needed
• Prescribing a medication to be taken at a time of day that is not optimal (e.g. diuretics at bedtime)
• Not prescribing a needed medication (e.g. a pain medication)
• Long-term use of opiate pain medication in patients other than those with terminal cancer

The Beers Criteria List

One of the two most widely used consensus criteria for safe medication use in older adults (the other is the Canadian criteria)

• PIMs=potentially inappropriate medications
• Composed of 53 medications of medication classes divided into 3 categories:
  1. PIMs and classes to avoid in older adults
  2. PIMs and classes to avoid in older adults with certain diseases that the drugs can exacerbate
  3. Medications to be used with caution in older adults (new)

These criteria included designations of the quality and strength of the evidence

• Quality of evidence is designated as high, moderate, or low
• Strength of recommendation is designated as strong, weak, or insufficient
• Medications are organized according to organ system or therapeutic category or drug
• The criteria also included rationale and recommendations
• The 2015 update is not a extensive as the 2012 update, but has 2 additions
  • Drugs for which dose adjustment is required based on renal function
  • Drug-drug interactions information

The risks of interventions provided and the speed of their implementation should be in direct proportion to the pain and dangerousness of the behaviors. Sometimes, the use of less precise medication interventions is needed initially in order to facilitate the investigation for underlying causes.  Download the Beer’s Criteria List.